Clinical, imaging, and endoscopic outcomes of children newly diagnosed with crohn's disease

Active Cooperative Agreement Awarded Last action

Award ID
U01DK134356
Recipient
Awarding agency
Obligated
$14,001,766

Award facts

Completion date 73% complete
Place of performance
Hartford, CT 06106, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Therapeutic goals in pediatric crohn's disease (CD) have shifted from clinical improvement or remission to endoscopic healing (EH) by ileocolonoscopy and transmural healing (TH) by magnetic resonance enterography (MRE). Patients achieving complete healing (CH, EH and TH) experience fewer hospitalizations or surgery. We hypothesize that specific pre-treatment clinical, radiologic, transcriptomic, genomic, and microbial factors along with attainment of targeted anti-TNF biologic exposure will be associated with the primary endpoint, CH, and the major secondary endpoints, EH and TH, 52 weeks after anti-TNF start. We will test this hypothesis in a prospective cohort study of 550 newly diagnosed pediatric-onset CD subjects treated with anti-TNF medication within 6 months of diagnosis guided by therapeutic drug monitoring (TDM). Aim 1. Evaluate putative associations and explore novel associations between CH and baseline measures of clinical and radiologic severity. We hypothesize that pre-treatment nutritional status, antimicrobial serologies, and MRE findings will be associated with year 1 CH. Formal hypothesis tests will be carried out with appropriately controlled type I error probabilities to confirm the predictive power of a set of pre- specified baseline measures using a logistic regression model based on the year 1 CH outcome. Aim 2. Evaluate putative associations and explore novel associations between anti-TNF drug levels, CH, and host and microbial genomic and transcriptomic factors. We hypothesize that pre-treatment gene expression signatures and microbial factors will be associated with early anti-TNF drug levels and year 1 CH. We will characterize the host genotype, baseline mucosal and longitudinal fecal microbial taxonomic profile, and baseline ileal and colon host transcriptome. Those variables identified as significantly associated will be candidates for the final prediction model determined in aim 3. Aim 3. Use a K-fold cross-validation procedure to determine the optimal predictive model of year 1 CH. We hypothesize that a model which includes host gene signatures and microbes will improve prediction of CH beyond one based on clinical and imaging factors alone. The model will include clinical and imaging predictors from aim 1 and host and microbial characteristics found to be potentially explanatory in aim 2. Impact. The proposed inception cohort study, cameo, will provide a robust platform to study factors that contribute to healing in pediatric CD that can then be translated into practice, as well as guiding future therapies targeting the host immune response and microbiota in patients unlikely to achieve healing. .

Transactions

Action Obligated Date
Amendment $0
Amendment $2,800,000
Amendment $2,800,000
Amendment $2,900,000
Amendment $168,861
Amendment $2,532,906
Amendment $0
Original award $2,799,999

Subawards

Subrecipient Amount Awarded
Emory University CAMEO Amendment $725,791
The Broad Institute, Inc. Clinical, imaging, and endoscopic outcomes of children newly diagnosed with Crohn's disease (CAMEO) $342,591
Childrens Hospital Medical Center $414,205
Subrecipient not on record $853,918
The Hospital For Sick Children Subrecipient will collaborate in the CAMEO study. Dr. Thomas Walters will serve as the site CO-I and will be a member of the Executive Steering Committee and… $27,668
Emory University Subrecipient will partner with PTE in the CAMEO project and Dr. Kugathasan will serve as MPI leadership role. Subrecipient will serve as the biorepository… $1,730,267
University Of North Carolina At Chapel Hill Subrecipient will collaborate on the CAMEO project. Dr. Couper and team at UNC will serve as the Data Coordinating Center (DCC) for the CAMEO project. $2,536,096
Childrens Hospital Medical Center Subrecipient will partner with PTE in the CAMEO project and Dr. Denson will serve as MPI leadership role. Subrecipient will focus on Aim 2 experiments and serve… $805,307
Subrecipient not on record Company will serve as a vendor for the CAMEO study and provide the services of Vipul Jairath, DPhil who will oversee the global Medical R&D initiatives and… $49,250

Quick answers

Who received award U01DK134356?

U01DK134356 was awarded to Connecticut Children's Medical Center by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on March 30, 2023.

How much is award U01DK134356 worth?

$14,001,766 has been obligated on U01DK134356.

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